ACCRF Research Update
July 2021
Board Leadership Additions
ACCRF is extremely fortunate to benefit from the guidance of some of the world’s leading oncologists on our Scientific Advisory Board as well as committed patient advocates on our Board of Directors (see our Leadership webpage). Thankfully, that tradition continues with one new addition to each governing body. Please welcome these two exceptional leaders to ACCRF!
Robert H. Vonderheide, MD, DPhil –
ACCRF Scientific Advisory Board

Dr. Vonderheide is the Director of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania and the John H. Glick, MD, Abramson Cancer Center’s Director Professor. He graduated from Oxford University as a Rhodes Scholar and Harvard Medical School. He completed training in internal medicine and medical oncology at the Massachusetts General Hospital and the Dana-Farber Cancer Institute.

Dr. Vonderheide is a distinguished scientist and clinician who has deciphered mechanisms of cancer immune surveillance and developed novel cancer therapeutics, particularly in pancreatic cancer. He is well-recognized for driving the development of agonist CD40 antibodies, now in later stage clinical trials as potential immune therapy of cancer. Dr. Vonderheide discovered telomerase as a universal tumor antigen and has led the efforts to develop telomerase vaccination for both therapy and the prevention of cancer in healthy individuals. He has helped lead a team to show that stereotactic radiation therapy in combination with dual checkpoint blockade represents a synergistic path for immune activation in cancer. Dr. Vonderheide merges his clinical investigations with rigorous studies in mouse models or other laboratory systems. Dr. Vonderheide has been continuously funded by the NCI, and his high-impact findings have been published in Nature, Science, Cell and the New England Journal of Medicine.
Bozho Todorich, MD, PhD –
ACCRF Board of Directors

Dr. Todorich is a practicing clinical ophthalmologist and retinal surgeon with a special interest in clinical and translational research. He graduated with honors from the Pennsylvania State University College of Medicine with an MD and a PhD in cell and molecular biology. He did his residency in ophthalmology at Duke University and subspecialty fellowship in retinal surgery at Beaumont Hospital. As a recipient of many national honors and an invited lecturer in his field, he has published extensively, is a scientific reviewer for a number of journals on retinal disease, and has been a principal and co-principal investigator on a number of clinical trials in ophthalmology. He has joined the ACCRF Board of Directors with a special interest in advancing clinical and translational research in ACC.
New Treatment Guidelines
The American Society of Clinical Oncology (ASCO) recently published its first treatment guidelines for salivary gland malignancies, including ACC. Among the authors were ACCRF’s Co-Founder Marnie Kaufman and six researchers who have collaborated closely with ACCRF. The guidelines are not meant to be rigid rules for patients and clinicians. Rather, as the authors state, “The clinician needs to consider how treatment might have acute and late toxicities for the patient affecting speech, taste, saliva, chewing, swallowing, lymphatic processes, nerves, teeth, facial bone structure and physical appearance. The clinician needs to discuss these potential impacts with the patient to balance the most effective treatment with the patient’s quality-of-life objectives.”

The guidelines cover pre-surgical evaluations, surgical procedures, post-operative radiation therapy, post-operative systemic therapy, patient follow-up, and treatment options for recurrent/metastatic patients. Each recommendation is accompanied by the quality of the evidence supporting it as well as the strength of the recommendation from the expert panel. Some recommendations are particularly noteworthy:

  • Recurrent or metastatic ACC patients for whom systemic therapy is appropriate may be offered a multitargeted tyrosine kinase inhibitor, such as Lenvatinib or Sorafenib, if a clinical trial is not available. Although not approved by regulatory authorities for ACC, these drugs appear to benefit some patients.

  • Post-operative radiation therapy should be offered to ACC patients following surgery given that overall survival benefit has been shown in all stages of disease. 

  • Particle therapy (proton, neutron and carbon ion radiation) may be used but currently there is insufficient evidence to show any benefit beyond photon radiation. More research is needed.

Previously, the National Comprehensive Cancer Network issued treatment guidelines for head and neck cancer that include some suggestions for salivary gland cancers. Last year’s update mentioned for the first time that Lenvatinib may be considered for recurrent or metastatic ACC patients, although effectiveness is not well established.

Later this year, the European Society of Medical Oncology (ESMO) is expected to issue guidelines for salivary gland cancer patients as well.
Clinical Trial Updates
The standard of care for ACC patients with progressing or inoperable tumors is not well established. Therefore, many such patients enroll in clinical trials to access promising though unproven treatments. Over the past several years, the number of clinical trials for ACC patients has increased dramatically with approximately twenty studies currently open (see Open Studies webpage). Here are some of the most recent developments:

  • All-Trans Retinoic Acid (ATRA) – In this recently published study, there were no partial responses (major tumor shrinkage of 30% or more). Eleven of sixteen evaluable patients (69%) had stable disease and the drug was very tolerable, suggesting that it may be worth exploring in combination with other more active drugs.

  • Apatinib/Rivoceranib – This multitargeted tyrosine kinase inhibitor has different names in China (Apatinib) and elsewhere (Rivoceranib). The first study of Apatinib in 65 ACC patients in Shanghai, China, was recently published, showing a partial response rate of 46% and moderate toxicity. Separately, an ASCO poster was recently presented of a study from the same group combining low-dose Apatinib with ATRA; the partial response rate among 16 patients was 19% and 81% had stable disease as best response. Lastly, a clinical trial of Rivoceranib in the United States and Korea recently completed enrollment; we expect preliminary findings to be reported in the fall or in the first half of next year.

  • CB-102 – A recent ASCO poster reported on 19 unselected ACC patients treated with this NOTCH inhibitor. Although there were no partial responses, 79% of patients had stable disease through week 8 and 58 % through week 20. Three patients with ACC harboring activating NOTCH alterations had stable disease for more than 6 months.

  • APG-115 – The clinical trial of this MDM2 inhibitor (with or without carboplatin) recently was put on hold while the preliminary results are being evaluated. A recent ASCO poster describes the study design. The study is expected to reopen soon.

Preliminary reports and final published results of all ACC clinical trials are available on the Completed Studies webpage. Patients may share these resources with their physicians in contemplating various treatment options. 
ACCRF Update Video
ACCRF’s friends at Salivary Gland Cancer UK have been hosting videoconferences that bring together patients and researchers. Although based in the United Kingdom, the group attracts patients from all over the world to its meetings. Earlier this year, ACCRF Executive Director Jeff Kaufman spoke to the group about ACCRF and its research priorities for this year. You may access the video replay at this link.
Attack ACC Dodgeball Challenge
ACC patient and dodgeball aficionado Shawn George wants to help our community get better treatments and a cure as fast as possible. So she has created the Attack ACC Dodgeball Challenge to spark donations to ACCRF. The rules are simple:

1. Create your own video with a partner.
2. Have the other person hold a sign that says ACC in front of their stomach.
3. Take 7-10 large steps away from them.
4. With a dodgeball or nerf ball, aim to hit the ACC sign in front of their stomach.
5. If you hit the sign you DONATE $10, if you miss you DONATE $20.
6. Nominate 3-5 friends to do the challenge within 24-48 hours by TAGGING them in the video you POST on social media.

More details on Shawn's wonderful initiative are included in this video. Spread the word and knock out ACC!